127 research outputs found

    A microRNA prognostic signature in patients with diffuse intrinsic pontine gliomas through non-invasive liquid biopsy

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    Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set (n = 23) as being able to stratify patients by risk of disease progression (log-rank p = 0.00014; HR = 7.99, 95% CI 2.38–26.87). When challenged in a separate validation set (n = 24), it confirmed its ability to predict progression (log-rank p = 0.00026; HR = 5.51, 95% CI 2.03–14.9). The value of our signature was also confirmed when overall survival was considered (log-rank p = 0.0021, HR = 4.12, 95% CI 1.57–10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient’s risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression

    GrailQuest & HERMES: Hunting for Gravitational Wave Electromagnetic Counterparts and Probing Space-Time Quantum Foam

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    Within Quantum Gravity theories, different models for space-time quantisation predict an energy dependent speed for photons. Although the predicted discrepancies are minuscule, GRB, occurring at cosmological distances, could be used to detect this signature of space-time granularity with a new concept of modular observatory of huge overall collecting area consisting in a fleet of small satellites in low orbits, with sub-microsecond time resolution and wide energy band (keV-MeV). The enormous number of collected photons will allow to effectively search these energy dependent delays. Moreover, GrailQuest will allow to perform temporal triangulation of high signal-to-noise impulsive events with arc-second positional accuracies: an extraordinary sensitive X-ray/Gamma all-sky monitor crucial for hunting the elusive electromagnetic counterparts of GW. A pathfinder of GrailQuest is already under development through the HERMES project: a fleet of six 3U cube-sats to be launched by 2021/22

    Development of the SIOPE DIPG network, registry and imaging repository : a collaborative effort to optimize research into a rare and lethal disease

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    Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Peer reviewe

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Il Concorso di Botticino. Vincono i giovani

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    Il progetto \ue8 stato premiato con il secondo posto nel concorso nazionale. Gli spazi sportivi sono stati pensati come vasche di movimenti di terra che minimizzassero il carattere disurbano intrinseco nelle recinzioni tecniche e completati con un progetto di verde che li trasformava in grandi stanze vegetali. Il costruito segnava invece un limite all'espansione edilizia verso lazona a parco sportivo

    Productive symptoms in right brain damage

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    Purpose of review: The purpose of this review is to summarize the more recent studies on productive symptoms from the neuropsychological, neurophysiological and anatomical points of view. The integration of these aspects may provide some clarifications on the cognitive impairments underpinning the main productive disorders, also contributing to better understand the normal functioning of the brain. Recent findings: Productive symptoms are closely associated to spatial neglect and are distinguished in relation to the part of space they manifest. The investigation of perseveration in extrapersonal space with different manipulations helps to understand the neuropathological mechanisms underlying this symptom. Anosognosia for hemiplegia and somatoparaphrenia may be considered as disorders of body representation (personal space). Recently it has been proposed that these disorders may be ascribed to an impairment of different levels of motor control. The identification of the anatomical correlates of these two disorders contributes to better understanding of their the cognitive nature. Summary: Productive behaviours have diverse clinical manifestations and may be induced by different mechanisms. Lesional studies are beginning to provide evidence for specific anatomical correlates of these disorders. Further investigations are needed to better understand to what extent productive symptoms can be disentagled from spatial neglect. These attempts may contribute to clarifying the role of the right hemisphere in monitoring spatial cognition
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